Sepsisli Kritik Hastalarda Erken Karaciğer Disfonksiyonunun Bir Göstergesi Olarak Hipomagnezemi

Year 2022, Volume: 24 Issue: 3, 299 - 306, 30.12.2022

Ömür İlban Ayşegül İlban

https://doi.org/10.18678/dtfd.1185917

Abstract

Amaç: Karaciğer disfonksiyonu, sepsiste gelişen inflamasyon ve hipoperfüzyonun neden olduğu erken bir bulgudur. Magnezyum eksikliği, immün strese karşı aşırı bir yanıta ve sepsiste inflamatuar doku hasarına katkıda bulunabilir. Bu çalışmada, sepsisli hastalarda serum magnezyum düzeyleri ile erken karaciğer disfonksiyonu (early liver dysfunction, ELD) arasındaki ilişkinin değerlendirilmesi amaçlandı.
Gereç ve Yöntemler: Sepsis gelişen 142 hasta karaciğer fonksiyonlarına göre ardışık organ yetmezliği değerlendirme (sequential organ failure assessment, SOFA) karaciğer alt skoru <2 olanlar (Non-ELD, n=72) ve SOFA karaciğer alt skoru ≥2 olanlar (ELD, n=70) olmak üzere iki gruba ayrıldı. Akut fizyoloji ve kronik sağlık değerlendirmesi (acute physiology and chronic health evaluation, APACHE) II skoru ve SOFA skoru dahil olmak üzere hastalık şiddeti, biyokimyasal belirleme ve mikrobiyolojik kültürler değerlendirildi.
Bulgular: ELD hastalarının APACHE II ve toplam SOFA skorları ELD olmayan hastalara göre daha yüksek iken, PaO2/FiO2 oranları anlamlı derecede düşüktü (her ikisi için p<0,001). Hipomagnezemi ve hipoalbüminemi ELD ile bağımsız şekilde ilişkiliydi (sırasıyla, OR: 6,55; %95 GA: 2,62-16,36 ve OR: 4,62; %95 GA: 1,35-15,84). ELD’yi öngörmede, serum magnezyum ve albümini için eğri altındaki alan sırasıyla 0,81 (%95 GA: 0,74-0,89; p<0,001) ve 0,70 (%95 GA: 0,61-0,79; p<0,001) idi. Tüm septik hastalardaki ölüm oranı, hipomagnezemi için %35,0 ve normomagnezemi için %25,6 idi (p=0,065). ELD hastalarındaki ölüm oranı hipomagnezemi için %34,1 ve normomagnezemi için %30,7 idi (p=0,415).
Sonuç: Magnezyum düzeylerindeki azalma, sepsisli kritik hastalarda artmış ELD oranları ile ilişkiliydi. Kabuldeki hipomagnezemi ne tüm sepsisli hastalarda, ne de ELD gelişenlerde mortaliteyi olumsuz etkilemedi.

Keywords

Kritik hasta, hipomağnezemi, karaciğer, mortalite, sepsis

Hypomagnesemia as a Predictor of Early Liver Dysfunction in Critically Ill Patients with Sepsis

Abstract

Aim: Liver dysfunction is an early finding caused by the inflammation and hypoperfusion developed in sepsis. Magnesium deficiency may contribute to an excessive response to immune stress and inflammatory tissue damage in sepsis. This study aimed to evaluate the relationship between serum magnesium levels and early liver dysfunction (ELD) in patients with sepsis.
Material and Methods: 142 patients who developed sepsis were divided into two groups according to their liver function, as sequential organ failure assessment (SOFA) hepatic subscore <2 (Non-ELD, n=72) and SOFA hepatic subscore ≥2 (ELD, n=70). The disease severity, including the acute physiology and chronic health evaluation (APACHE) II score and the SOFA score, biochemical determination, and microbiological cultures were evaluated.
Results: ELD patients presented APACHE II and total SOFA scores higher than Non-ELD patients, while PaO2/FiO2 ratios were significantly lower (both p<0.001). Hypomagnesemia and hypoalbuminemia were independently associated with ELD (OR: 6.55, 95% CI: 2.62-16.36, and OR: 4.62, 95% CI: 1.35-15.84, respectively). To predict ELD, the area under the curve was 0.81 (95% CI: 0.74-0.89, p<0.001) and 0.70 (95% CI, 0.61-0.79; p<0.001) for serum magnesium and albumin, respectively. The mortality rate in all septic patients was 35.0% for hypomagnesemia and 25.6% for normomagnesemia (p=0.065). The mortality rate in ELD patients was 34.1% for hypomagnesemia and 30.7% for normomagnesemia (p=0.415).
Conclusion: The reduction of magnesium levels was associated with increased rates of ELD in critically ill patients with sepsis. Admission hypomagnesemia did not adversely affect mortality neither in all sepsis patients nor in those who developed ELD.

Keywords

Critically ill, hypomagnesemia, liver, mortality, sepsis

References

• Napolitano LM. Sepsis 2018: definitions and guideline changes. Surg Infect (Larchmt). 2018;19(2):117-25.
• Lelubre C, Vincent JL. Mechanisms and treatment of organ failure in sepsis. Nat Rev Nephrol. 2018;14(7):417-27.
• Canabal JM, Kramer DJ. Management of sepsis in patients with liver failure. Curr Opin Crit Care. 2008;14(2):189-97.
• Yan J, Li S, Li S. The role of the liver in sepsis. Int Rev Immunol. 2014;33(6):498-510.
• Tong GM, Rude RK. Magnesium deficiency in critical illness. J Intensive Care Med. 2005;20(1):3-17.
• Chen M, Sun R, Hu B. The influence of serum magnesium level on the prognosis of critically ill patients. Chin Crit Care Med. 2015;27(3):213-7. Chinese.
• Blache D, Devaux S, Joubert O, Loreau N, Schneider M, Durand P, et al. Long-term moderate magnesium-defcient diet shows relationships between blood pressure, infammation and oxidant stress defense in aging rats. Free Radic Biol Med. 2006;41(2):277-84.
• Gunther T, Hollriegl V. Increased lipid peroxidation in liver mitochondria from Mg-deficient rats. J Trace Elem Electrolytes Health Dis. 1989;3(4):213-6.
• Dibaba DT, Xun P, He K. Dietary magnesium intake is inversely associated with serum C-reactive protein levels: meta-analysis and systematic review. Eur J Clin Nutr. 2015;69(3):409.
• Simental-Mendia LE, Sahebkar A, Rodriguez-Moran M, Zambrano-Galvan G, Guerrero-Romero F. Effect of magnesium supplementation on plasma C-reactive protein concentrations: a systematic review and meta-analysis of randomized controlled trials. Curr Pharm Des. 2017;23(31):4678-86.
• Hong MK, Hu LL, Zhang YX, Xu YL, Liu XY, He PK, et al. 6-Gingerol ameliorates sepsis-induced liver injury through the Nrf2 pathway. Int Immunopharmacol. 2020;80:106196.
• Lin CY, Tsai PS, Hung YC, Huang CJ. L-type calcium channels are involved in mediating the anti-inflammatory effects of magnesium sulphate. Br J Anaesth. 2010;104(1):44-51.
• El-Tanbouly DM, Abdelsalam RM, Attia AS, Abdel-Aziz MT. Pretreatment with magnesium ameliorates lipopolysaccharide-induced liver injury in mice. Pharmacol Rep. 2015;67(5):914-20.
• Kramer L, Jordan B, Druml W, Bauer P, Metnitz PG. Incidence and prognosis of early hepatic dysfunction in critically ill patients--a prospective multicenter study. Crit Care Med. 2007;35(4):1099-104.
• Dugar S, Choudhary C, Duggal A. Sepsis and septic shock: Guideline-based management. Cleve Clin J Med. 2020;87(1):53-64.
• Vatsalya V, Gala KS, Mishra M, Schwandt ML, Umhau J, Cave MC, et al. Lower serum magnesium concentrations are associated with specific heavy drinking markers, pro-inflammatory response and early-stage alcohol-associated liver injury. Alcohol Alcohol. 2020;55(2):164-70.
• Cecconi M, Evans L, Levy M, Rhodes A. Sepsis and septic shock. Lancet. 2018;392(10141):75-87.
• Ghenu MI, Dragoş D, Manea MM, Ionescu D, Negreanu L. Pathophysiology of sepsis-induced cholestasis: a review. JGH Open. 2022;6(6):378-87.
• Wang P, Ba ZF, Chaudry IH. Hepatocellular dysfunction occurs earlier than the onset of hyperdynamic circulation during sepsis. Shock. 1995;3(1):21-6.
• Kluge M, Tacke F. Liver impairment in critical illness and sepsis: the dawn of new biomarkers? Ann Transl Med. 2019;7(Suppl 8):S258.
• Brandorg L, Goldman I. Bacterial and miscellaneous infections of the liver. In: Zakim D, Boyer TD, editors. Hepatology, a textbook of the liver. 1st ed. Philadelphia: W.B. Saunders; 1990. p.1086-98.
• Woźnica EA, Inglot M, Woźnica RK, Lysenko L. Liver dysfunction in sepsis. Adv Clin Exp Med. 2018;27(4):547-51.
• Limaye CS, Londhey VA, Nadkart MY, Borges NE. Hypomagnesemia in critically ill medical patients. J Assoc Physicians India. 2011;59:19-22.
• Noronha LJ, Matuschak GM. Magnesium in critical illness: metabolism, assessment, and treatment. Intensive Care Med. 2002;28(6):667-79.
• Lee CY, Jan WC, Tsai PS, Huang CJ. Magnesium sulfate mitigates acute lung injury in endotoxemia rats. J Trauma. 2011;70(5):1177-85.
• Rodriguez-Hernandez H, Cervantes-Huerta M, Rodriguez-Moran M, Guerrero-Romero F. Oral magnesium supplementation decreases alanine aminotransferase levels in obese women. Magnesium Res. 2010;23(2):90-6.
• Karandish M, Tamimi M, Shayesteh AA, Haghighizadeh MH, Jalali MT. The effect of magnesium supplementation and weight loss on liver enzymes in patients with nonalcoholic fatty liver disease. J Res Med Sci. 2013;18(7):573-9.
• Sayeed MM, Zhu M, Maitra SR. Alterations in cellular calcium and magnesium during circulatory/septic shock. Magnesium. 1989;8(3-4):179-89.
• Calviello G, Ricci P, Lauro L, Palozza P, Cittadini A. Mg deficiency induces mineral content changes and oxidative stress in rats. Biochem Mol Biol Int. 1994;32(5):903-11.
• George GA, Heaton FW. Effect of magnesium deficiency on energy metabolism and protein synthesis by liver. Int J Biochem. 1978;9(6):421-5.
• Singer M, De Santis V, Vitale D, Jeffcoate W. Multiorgan failure is an adaptive, endocrine-mediated, metabolic response to overwhelming systemic inflammation. Lancet. 2004;364(9433):545-8.
• Jensen JS, Peters L, Itenov TS, Bestle M, Thormar KM, Mohr TT, et al. Biomarker-assisted identification of sepsis-related acute liver impairment: a frequent and deadly condition in critically ill patients. Clin Chem Lab Med. 2019;57(9):1422-31.
• Nesseler N, Launey Y, Aninat C, White J, Corlu A, Pieper K, et al. Liver dysfunction is associated with long-term mortality in septic shock. Am J Respir Crit Care Med. 2016;193(3):335-7.
• Brun-Buisson C, Meshaka P, Pinton P, Vallet B. EPISEPSIS: A reappraisal of the epidemiology and outcome of severe sepsis in French intensive care units. Intensive Care Med. 2004;30(4):580-8.
• Blanco J, Muriel- Bombín A, Sagredo V, Taboada F, Gandía F, Tamayo L, et al. Incidence, organ dysfunction and mortality in severe sepsis: a Spanish multicentre study. Crit Care. 2008;12(6):R158.
• Jarrar D, Wang P, Chaudry IH. Hepatocellular dysfunction-basic considerations. In: Holzheimer RG, Mannick JA, editors. Surgical treatment: evidence-based and problem-oriented. Munich: Zuckschwerdt; 2001.
• Kaffarnik MF, Lock JF, Vetter H, Ahmadi N, Lojewski C, Malinowski M, et al. Early diagnosis of sepsis-related hepatic dysfunction and its prognostic impact on survival: a prospective study with the LiMAx test. Crit Care. 2013;17(5):R259.
• Soliman HM, Mercan D, Lobo SS, Mélot C, Vincent JL. Development of ionized hypomagnesemia is associated with higher mortality rates. Crit Care Med. 2003;31(4):1082-7.
• Chernow B, Bamberger S, Stoiko M, Vadnais M, Mills S, Hoellerich V, et al. Hypomagnesemia in patients in postoperative intensive care. Chest. 1989;95(2):391-7.
• Kvarantan T, Bosman RJ, Oudemans-van Straaten HM. Severe hypomagnesaemia in the intensive care unit. Neth J Crit Care. 2014;18(5):23-8.